Well-treated hypertensive but otherwise healthy people demonstrated cerebral atrophy on magnetic resonance imaging (MRI), manifested by lateral ventricle enlargement and left hemisphere atrophy. Brain glucose utilization as measured with positron emission tomography was reduced in territories of perforating arteries (thalamus and lenticular nucleus bilaterally). Well-treated hypertensives also had an abnormal circadian blood pressure variation, although their average 24 hour ambulatory blood pressure was well controlled compared with healthy controls. We compared the clinical course, cerebral morphometabolic data, and postmortem examination in dementia of the Alzheimer type (DAT) patients with and without white matter change (leukoencephalopathy) on MRI. Extensive white matter changes were found in patients with slowly progressive dementia clinically indistinguishable from DAT. These patients differed from DAT patients without white matter change in their pattern of cerebral glucose consumption, suggesting that the white matter change is a process different from Alzheimer's disease. Postmortem studies of brains of three such patients showed Alzheimer's disease and severe amyloid angiopathy. In healthy subjects with white matter changes on MRI, the volume of the changes correlated with increased ventricular volume, reduced brain volume, and reduced cognitive scores. Subjects with greater than 0.5 % white matter hyperintensity volume also had lower whole brain and frontal lobe glucose metabolism, higher systolic blood pressure, and larger ventricular volume than age-matched controls